The main objective of this study is to increase understanding of the natural history of injection drug use, with a specific focus on long-term injection cessation, using data from the AIDS Link to the IntraVenous Experience (ALIVE) study, a community-based cohort of injection drug users (IDUs) in Baltimore, Maryland. The majority of HIV prevention strategies directed at IDUs focus on reducing the frequency and harms associated with injection drug use. While these efforts are important, the ultimate goal of HIV prevention for IDUs is long-term injection cessation. Previous research on injection cessation has focused primarily on individual-level factors that predict short periods of cessation (i.e. 6 months to one year). Studies of individual factors associated with short-term cessation do not take into account the factors that maintain longer periods of cessation or the broader social factors that create environments that encourage and sustain cessation. Since addiction is often characterized by periods of abstinence and relapsed use within relatively short time spans, predictors of short-term cessation may differ from predictors of long-term cessation and short-term cessation may not lead to long term recovery for all IDUs. The current study will be nested within the ALIVE study, which has enrolled and followed nearly 4,000 predominantly African-American IDUs since 1988 in Baltimore City. The specific aims of this study are: 1) To characterize the longitudinal patterns of injection and non-injection drug use, including long term injection cessation, among IDUs;2) To identify individual-level predictors of long-term injection cessation among IDUs;and 3) To determine neighborhood- level predictors of long-term cessation of injection among IDUs. We propose a combination of qualitative, longitudinal, and multilevel analyses to investigate long-term injection cessation. Each aim will be explored qualitatively with iterative in-depth interviews with IDUs who have achieved long-term cessation. The quantitative analysis will begin by using the rich longitudinal data collected in the ALIVE study to determine the frequency of long-term cessation, defined as no injection for at least 3 years, as well as other injection and non-injection drug use patterns from 1988 to 2007. We will employ a nested case-control design to determine the longitudinal predictors of long-term cessation, as well as factors that maintain cessation, at the individual- level. Finally we will conduct multilevel analyses using Geographic Information System (GIS) software to link individual residential data to US Census and other administrative neighborhood-level data to examine the neighborhood characteristics (e.g. socio-economic disadvantage) in Baltimore City that promote and maintain long-term injection cessation. The proposed study will inform HIV and substance use interventions aimed at promoting and maintaining long-term injection cessation among IDUs. Project Narrative. The main objective of this study is to increase understanding of the natural history of injection drug use, with a specific focus on long-term injection cessation. We propose a combination of qualitative, longitudinal, and multilevel analyses to investigate the individual and neighborhood-level predictors of long-term injection cessation among injection drug users (IDUs). The proposed study will inform HIV prevention and substance use interventions aimed at promoting and maintaining long-term injection cessation among IDUs.